Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

Addisu Getie; Afework Edmealem; Tegene Atamenta Kitaw

doi:10.1371/journal.pone.0321586

. 2025 Apr 10;20(4):e0321586. doi: 10.1371/journal.pone.0321586

Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

Addisu Getie ^1,^*, Afework Edmealem ¹, Tegene Atamenta Kitaw ²

Editor: Usama Waqar³

PMCID: PMC12007617 PMID: 40208911

Abstract

IntroductionCancer is a leading cause of global morbidity and mortality, significantly impairing patients’ quality of life (QoL). Integrated Palliative Care (IPC) has been proposed as a holistic approach to enhance quality of life by addressing patients’ physical, emotional, and psychosocial needs. While some studies suggest Integrated Palliative Care improves quality of life more than standard care, the evidence remains inconclusive. This systematic review and meta-analysis aim to evaluate the comparative impact of Integrated Palliative Care versus standard care on the quality of life in cancer patients.

MethodsA comprehensive search of databases including PubMed, Cochrane Library, and Embase was conducted. We selected randomized controlled trials (RCTs) comparing Integrated Palliative Care and standard care for cancer patients, focusing on the quality of life as measured by validated tools such as the EORTC QLQ-C30 and FACT-G. Data were pooled using a random-effects model to account for study heterogeneity. Subgroup and sensitivity analyses were also performed.

ResultsNine randomized controlled trials involving 1,794 patients met the inclusion criteria. Meta-analysis showed that Integrated Palliative Care significantly improved quality of life compared to standard care (SMD = 3.25; 95% CI: 1.20–5.30; p < 0.001). Studies conducted in Asia showed the highest standardized mean difference (SMD = 6.15; 95% CI: 3.07–9.23; p < 0.001), followed closely by studies from Africa (SMD = 6.0; 95% CI: 5.13–6.87; p < 0.001), compared to those from other regions. Similarly, research focusing on lung cancer patients showed the greatest standardized mean difference of (SMD = 6.15; 95% CI: 3.07–9.23; p < 0.001) relative to other cancer types. Furthermore, studies involving newly diagnosed cancer patients recorded the highest standardized mean difference of (SMD = 5.69; 95% CI: 4.57–6.80; p < 0.001).

ConclusionIntegrated Palliative Care significantly enhances the quality of life in cancer patients compared to standard care. These findings support integrating Integrated Palliative Care into oncology practices to provide comprehensive, patient-centered care that addresses both physical and emotional needs. Further research should explore long-term benefits across diverse populations.

Introduction

Cancer remains one of the leading causes of morbidity and mortality worldwide, profoundly impacting patients’ quality of life (QoL) [1]. With an increasing incidence of cancer cases, the need for effective care strategies that address not only the medical but also the psychosocial and emotional needs of patients has become paramount. Integrated Palliative Care (IPC) is a multidisciplinary approach to palliative care that combines medical, psychological, social, and spiritual support to enhance the quality of life for cancer patients. This model involves collaboration among healthcare providers, including oncologists, palliative care specialists, nurses, social workers, and spiritual care providers, to deliver comprehensive care that addresses the physical, emotional, and social needs of patients. Standard care refers to the usual treatment provided for cancer patients, which typically involves conventional cancer therapies such as chemotherapy, radiotherapy, and surgery, without the integration of specialized palliative care services [2,3]. Integrated palliative care (IPC) has emerged as a comprehensive approach designed to improve the QoL of cancer patients by providing multidisciplinary support and addressing various aspects of their well-being. By integrating symptom management, psychosocial support, and advanced care planning, IPC aims to enhance the overall experience of patients during the continuum of care [4].

Research indicates that IPC can significantly alleviate pain, anxiety, and depression, which are prevalent among cancer patients [5]. However, the effectiveness of IPC compared to standard care in enhancing QoL remains a topic of debate. Standard care typically focused on curative treatment, often overlooks the holistic needs of patients, which may lead to suboptimal patient experiences and increased distress [6]. Thus, there is a critical need to evaluate the comparative impact of IPC versus standard care on QoL outcomes among cancer patients through systematic analysis of randomized controlled trials (RCTs).

Despite the growing body of literature on the subject, previous studies have yielded mixed results, highlighting a gap in consensus regarding the efficacy of IPC in improving QoL [7]. Several studies have demonstrated that integrated palliative care (IPC) significantly improves patient outcomes, particularly in areas such as symptom management and emotional support [8]. A systematic review and meta-analysis of RCTs will help to consolidate the available evidence and provide clearer insights into the potential benefits of IPC over standard care in this patient population.

This systematic review builds on the growing body of literature that has explored the impact of Integrated Palliative Care (IPC) on the quality of life (QoL) of cancer patients, acknowledging the important contributions of earlier studies. While prior research has provided valuable insights, many have focused on specific populations or small sample sizes, and their findings have been mixed, leaving some gaps in understanding. Our study seeks to address these gaps by synthesizing evidence from the most recent randomized controlled trials (RCTs), which offer more rigorous and reliable data. By including a broader range of RCTs, this review aims to provide an updated, comprehensive analysis of the comparative impact of IPC versus standard care across diverse cancer types and settings.

The unique contribution of our study lies in its ability to incorporate the latest evidence, allowing for a more nuanced understanding of the outcomes of IPC on QoL in cancer patients. We also explored variations in the effectiveness of IPC based on different parameters including regional contexts, cancer site, and patient category providing a global perspective on its role in palliative care. By synthesizing this contemporary data, this review offered robust and evidence-based conclusions that can directly inform clinical practice, healthcare policies, and the integration of IPC into routine oncology care. Ultimately, we hope to further establish IPC as an essential component in improving the QoL of cancer patients and ensure that its integration into standard oncology practice is strongly supported by the latest research.

Method

The study protocols

The results of this systematic review and meta-analysis were reported using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) reporting guideline (S1 Table in S1 Text).

Search strategy

For this systematic review and meta-analysis, a comprehensive search strategy was employed to identify relevant randomized controlled trials (RCTs) comparing the impact of integrated palliative care with standard care on the quality of life in cancer patients. The search was conducted across multiple databases including PubMed, MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science. Search terms included a combination of keywords and Medical Subject Headings (MeSH) related to palliative care, standard care, cancer, quality of life, and randomized controlled trials. Boolean operators (AND, OR) were used to refine the search, and filters were applied to limit the studies to RCTs published in English for the past ten years. Additionally, references of selected articles were hand-searched to identify any further relevant studies. Duplicates were removed, and the selection process was following the PRISMA guidelines. Articles published until September 2024 were included in the search. The last date for searching was September 15, 2024

Eligibility criteria

For this systematic review and meta-analysis, the inclusion criteria were centered on randomized controlled trials (RCTs) that had compared the effects of integrated palliative care with standard care in cancer patients, with a particular emphasis on evaluating their impact on patients’ quality of life. We included only RCTs because they are regarded as the gold standard for assessing the effectiveness of interventions, offering high-quality evidence with a low risk of bias. By focusing on RCTs, we sought to ensure the reliability and strength of our findings, thereby strengthening the validity of our conclusions about the impact of integrated palliative care on the quality of life in cancer patients. Studies were included if they involved adult cancer patients of any cancer type and provided quantitative data on quality of life using standardized, validated assessment tools. Only peer-reviewed studies published in English within the last ten years, from any geographical region, were considered. The exclusion criteria, on the other hand, ruled out non-randomized studies, including observational studies, case reports, conference proceedings, and review articles. Additionally, studies that did not specifically compare integrated palliative care to standard care or failed to report measurable quality-of-life outcomes were excluded. Furthermore, trials that exclusively focused on pediatric cancer patients, those involving non-cancer populations, or those that were not available in full-text format were also excluded from the review.

Outcome measurement of the study

The outcome measurement of this global systematic review and meta-analysis of randomized controlled trials focused on the quality of life (QoL) in cancer patients, as assessed by standardized and validated instruments, such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy-General (FACT-G) scale. These tools were consistently used across studies to capture comprehensive dimensions of QoL, including physical, emotional, and social well-being. Secondary outcomes, including symptom management (e.g., pain, fatigue, and psychological distress), were evaluated using tools like the Edmonton Symptom Assessment System (ESAS) to provide a detailed understanding of patient-reported symptom burden.

Data collection and quality assessment

For the systematic review and meta-analysis titled “Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials,” data collection was conducted by systematically searching multiple electronic databases, including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase, for randomized controlled trials (RCTs) published in the last ten years. The search was supplemented by manual screening of reference lists from relevant studies to ensure comprehensive coverage. Studies that met predefined inclusion criteria, such as those involving cancer patients receiving either integrated palliative care or standard care, were selected. Data were extracted using a standardized form, capturing study characteristics, interventions, outcomes, and quality of life measures. The Cochrane Risk of Bias Tool was employed to assess the methodological quality of included trials, focusing on randomization processes, blinding, and completeness of outcome data. Studies were categorized as high, moderate, or low risk of bias based on these assessments. A study is categorized as high risk if there are significant concerns in any of the key areas (randomization, blinding, completeness of data) that could potentially impact the study’s results. It is classified as a moderate risk if there are some issues, but these are unlikely to fully compromise the findings. A study is considered low risk if it is methodologically robust and free from major biases. The quality of the included randomized controlled trials (RCTs) was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist, focusing on key aspects of study design such as randomization, allocation concealment, blinding, and follow-up completeness. This ensured a systematic and rigorous assessment of methodological quality [9]. Data extraction and quality assessment were performed independently by two reviewers to minimize bias, with disagreements resolved through consensus or consultation with a third reviewer. Additionally, we used Covidence software to facilitate the screening and selection of studies in our systematic review. The use of this tool helped streamline the process and ensured a more efficient and transparent review. This rigorous process ensured the reliability and validity of the findings, adhering to recent guidelines for conducting systematic reviews and meta-analyses in health care research [10,11].

Data synthesis and analysis

The overall global comparative impact of integrated palliative care vs. standard care on the quality of life in cancer patients was measured using the standardized mean difference and pooled using a weighted inverse variance random-effects model at 95%CI [12]. The data were extracted and cleaned using Microsoft Excel spreadsheets and exported to STATA version 11.0 (Stata Corporation, College Station, Texas) software for analysis. The heterogeneity of the studies was assessed using the Cochrane Q test and I² with its corresponding p-value [13]. To examine the source of heterogeneity, subgroup analysis, sensitivity analysis, and meta-regression were carried out. In addition, the presence of publication bias was evaluated by using Egger’s test and funnel plot [14]. Finally, a statistical test with a P-value of less than 0.05 was considered statistically significant.

Ethics approval and consent to participate

Not applicable.

Results

In this systematic review and meta-analysis, a comprehensive search was conducted across multiple databases using targeted keywords, yielding a total of 1,141 RCTs. However, a large portion of these studies was excluded during the screening process for various reasons. Many were eliminated due to duplication, failure to report outcomes relevant to the study, inadequate methodological quality, or lack of access to the full text. Furthermore, after a detailed evaluation of titles and abstracts, additional RCTs were excluded as they did not meet the inclusion criteria. Following this rigorous screening process, a final selection of nine RCT studies was included for final analysis, as they satisfied all the criteria for inclusion in the review (Fig 1).

Study characteristics

Nine randomized controlled trials involving 1,794 patients met the inclusion criteria conducted globally, with studies spanning Europe [15–20], Africa [21], North America [22], and Asia [23] between 2015 and 2023 were included. These trials evaluated the comparative impact of integrated palliative care (IPC) versus standard care (SC) on the quality of life (QoL) in cancer patients. The types of cancers varied widely, including lung, gastrointestinal, breast, and reproductive organ cancers, with patient populations encompassing both newly diagnosed and patients on follow-up. Sample sizes across the studies ranged from 57 to 280 participants, providing a robust comparison between IPC and SC groups. Quality of life outcomes were commonly assessed using validated tools, and the follow-up periods ranged from several months to over a year. The studies consistently showed a positive impact of IPC on patient satisfaction, symptom management, and overall quality of life, especially in patients who were on follow up, supporting the integration of palliative care into standard treatment protocols globally (Table 1).

Table 1. Study characteristics on RCTs done to evaluate the comparative impact of integrated palliative care vs. standard care on the quality of life in cancer patients.

Author and publication year	Study setting	Site of cancer	Patient category	Follow up duration in month	Sample size of IG	Sample size of CG	Mean QoL of cancer patients who received integrated palliative care	Mean QoL of cancer patients who received standard care	SD QoL of cancer patient who received integrated palliative care	SD QoL of cancer patient who received standard care	Name of data extractor	Date of data extraction	Eligibility to be included based on JBI
Franciosi V et al, 2019	Europe	Lung and GI	On follow up	3	113	105	70.1	69.6	15.5	15.5	Addisu Getie	Sep.3, 2024	Yes
Marie A et al, 2015	Europe	Breast, GI, reproductive organ	On follow up	3	29	28	12.6	11.7	1.9	1.9	Addisu Getie	Sep. 5, 2024	Yes
Reid EA et al, 2022	Africa	All	Newly diagnosed	3	42	53	24	18.0	2.5	1.8	Addisu Getie	Sep.6, 2024	Yes
Vanbutsele G et al, 2018	Europe	All	On follow up	3	92	94	61.98	54.4	24	25.3	Addisu Getie	Sep.8, 024	Yes
Chen M et al, 2023	Asia	Lung only	Newly diagnosed	6	140	140	117.81	111.7	11.15	14.9	Addisu Getie	Sep.11, 2024	Yes
Groenveld M et al, 2017	Europe	All	On follow up	2	145	152	57.6	59.9	22.3	22.5	Afework Edmealem	Sep.11, 2024	Yes
Slama O et al, 2020	Europe	All	On follow up	6	60	66	66.7	62.8	25.4	25	Afework Edmealem	Sep.13, 2024	Yes
Jennifer S et al, 2016	North America	Lung and GI	Newly diagnosed	3	175	175	81	77.7	13.3	12.9	Afework Edmealem	Sep.14,2024	Yes
Vanbutsele G et al, 2020	Europe	Breast, GI, reproductive organ	On follow up	3	91	94	61	58.0	18.6	20.1	Afework Edmealem	Sep.15,2024	Yes

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CG: Control Group, IG: Intervention Group, GI: Gastrointestinal, JBI: Joanna Briggs Institute, SD: Standard Deviation, all: RCTs that included cancer patients of various types, with the study populations consisting of cancer patients regardless of the cancer site.

Risk of bias and quality assessment

We conducted a comprehensive risk of bias and quality assessment for the included randomized controlled trials (RCTs) using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist and the Cochrane Risk of Bias (RoB 2) tool, represented with a traffic light system. The JBI checklist was employed to evaluate study design aspects, including randomization, allocation concealment, blinding, and completeness of follow-up, ensuring a structured appraisal of methodological rigor (S2 Table in S1 Text). The Cochrane RoB 2 tool provided a detailed assessment across domains such as bias in randomization, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Each domain was categorized as “low risk,” “some concerns,” or “high risk,” and visually summarized using traffic light plots to highlight the distribution of risk levels (S1 Fig in S1 Text). This dual approach allowed for a robust evaluation, ensuring transparency and reliability in interpreting the quality of the evidence base.

Meta-analysis

Impact of integrated palliative care.

The study comparing the impact of integrated palliative care versus standard care on the quality of life in cancer patients showed a significant improvement in the integrated palliative care group, with a standard mean difference (SMD = 3.25; 95% CI: 1.20–5.30; p < 0.001). This indicates that patients receiving integrated palliative care experienced a notable enhancement in their quality of life compared to those receiving standard care (Fig 2).

Heterogeneity and investigation of the source of heterogeneity.

Due to the presence of heterogeneity (I² =82.94%) among the included studies, a subgroup analysis, meta-regression, and sensitivity analysis were conducted to explore the potential source of variations. The moderators considered to conduct subgroup analysis and meta-regression were the continent where the studies were conducted, the site of cancer, the patient category, and follow up duration. These analyses aimed to identify whether the observed variations in the outcomes could be attributed to these factors, providing a clearer understanding of the differential impact of the interventions across diverse populations and cancer types. A subgroup analysis was conducted based on the study settings, categorizing the studies by their respective regions: Europe, Africa, Asia, and North America. Thus, studies from Asia reported the highest standardized mean difference (SMD = 6.15; 95% CI: 3.07–9.23; p < 0.001), followed closely by studies conducted in Africa (SMD = 6.00; 95% CI: 5.13–6.87; p < 0.001), compared to those from other continents (Fig 3). Similarly, a subgroup analysis was conducted based on cancer type. The analysis revealed that studies involving lung cancer patients exhibited the highest standardized mean difference (SMD = 6.15; 95% CI: 3.07–9.23; p < 0.001) (Fig 4). Additionally, a subgroup analysis was performed based on patient categories, specifically newly diagnosed cancer patients and those on follow-up. Studies involving newly diagnosed cancer patients showed the highest standardized mean difference (SMD = 5.69; 95% CI: 4.57–6.80; p < 0.001) (Fig 5). Furthermore, subgroup analysis was conducted based on the duration of follow-up, which included follow-up periods of two, three, and six months. Studies with six months of follow-up period showed the highest standardized mean difference (SMD = 5.90; 95% CI: 2.99–8.81) (Fig 6). The findings indicate that integrating palliative care has a significantly greater impact on patients from Asia and Africa, as well as those with lung cancer and individuals who are newly diagnosed. The meta-regression results indicated that the moderators, continent, site of cancer, and follow up duration, were not significant sources of heterogeneity, with P-values of 0.261, 0.58, 0.231, respectively. However, the patient category emerged as a potential source of heterogeneity, as indicated by a P-value of 0.019. The sensitivity analysis, conducted using a one-point leave-out method, revealed no influential studies, as all remained within the confidence interval of 1.20–5.30. This suggests that the overall results are robust, and no single study disproportionately influenced the findings (Fig 7).

Publication bias.

The funnel plot demonstrated a symmetrical distribution of the included studies, indicating the absence of significant publication bias. Additionally, Egger’s test yielded a non-significant result (P = 0.8775), further confirming that there is no strong evidence of bias affecting the overall findings (Fig 8). The trim and fill analysis confirmed the absence of publication bias, as the mean difference between the observed studies and the observed plus imputed studies remained consistent. There was no significant change in the mean difference, further validating the robustness of the results and the lack of bias in the included studies.

Discussion

This study presented a significant positive impact of integrated palliative care on the quality of life of cancer patients compared to standard care (SMD = 3.25; 95% CI: 1.20–5.30; p < 0.001). This is because IPC is attributed to its holistic approach, which addresses not only physical symptoms but also emotional, social, and spiritual needs. Integrated palliative care provides tailored support from a multidisciplinary team, offering pain and symptom management, psychological counseling, and assistance with treatment decisions [24]. This comprehensive care enhances patients’ ability to cope with the physical and psychological burden of cancer, leading to improved overall well-being. Moreover, early intervention in symptom control and emotional support reduces distress and enhances quality of life, especially in high-burden cancers like lung cancer, where patients experience intense symptoms [2]. This approach contrasts with standard care, which primarily focuses on treating the disease and may overlook the broader quality-of-life issues faced by patients. This finding aligns with existing literature that consistently demonstrates the effectiveness of palliative care in improving various health-related quality of life (HRQOL) dimensions in cancer patients, including physical, emotional, and social well-being. Comparatively, a systematic review also reported significant HRQOL improvements with palliative care integration, but it highlighted that benefits were more consistent for psychosocial outcomes rather than physical functioning [25]. Similarly, Zimmermann et al. (2014) found that early integration of palliative care improved both quality of life and mood, with lung cancer patients particularly benefiting from early interventions, corroborating the results of this study where lung cancer showed the highest SMD [26].

The overall assessment revealed that the risk of bias was predominantly low across the included RCTs. Most studies demonstrated rigorous randomization and allocation concealment processes, with effective blinding of participants, assessors, and personnel. These findings align with similar assessments conducted in prior systematic reviews, where comprehensive appraisal tools such as JBI and RoB 2 consistently contributed to improving the confidence in synthesized results [27]. The low risk of bias across studies suggests that the included trials provide a robust evidence base for assessing the comparative impact of integrated palliative care versus standard care on the quality of life in cancer patients.

Sub-group analysis showed that the impact of palliative care varied by region, with Asian and African studies reporting the highest standard mean difference. This could be attributed to the fact that, in many African and Asian countries, access to cancer care services, especially curative treatments such as radiotherapy and chemotherapy is often constrained by economic and infrastructural limitations [28]. Integrated palliative care programs help address this gap by prioritizing symptom control, psychological support, and end-of-life care, which significantly improve patients’ quality of life [24]. Moreover, these programs in Africa and Asia often adopt a holistic approach, catering to the physical, emotional, social, and spiritual needs of patients. By incorporating culturally sensitive practices that align with local traditions and values, they enhance satisfaction for both patients and their families [29]. The type of cancer also impacted the outcomes, with lung cancer patients exhibiting the greatest improvement in quality of life. This could be because lung cancer is often diagnosed at advanced stages when curative treatment options are limited, and patients face a significant burden of severe symptoms [30]. Integrated palliative care effectively mitigates these symptoms through targeted approaches, such as pharmacological pain management, oxygen therapy for breathlessness, and psychological support, resulting in notable quality-of-life enhancements [25]. Moreover, lung cancer patients frequently endure a heightened psychological burden due to the stigma surrounding smoking and the disease’s rapid progression. Integrated palliative care programs address these challenges by providing psychosocial support, counseling, and involving families, which helps reduce anxiety and depression while improving emotional well-being [31–33]. The results of this study also revealed that studies with a six-month follow-up period had the highest standardized mean difference. This could be because a longer follow-up period provides more time to observe the intervention’s effects, leading to more robust and dependable outcome estimates. Moreover, extended follow-up periods can capture long-term effects that shorter durations may overlook, such as the sustainability of results or delayed negative outcomes [34].

Although subgroup, meta-regression, and sensitivity analyses were performed to address heterogeneity, the observed variation may be attributed to other factors such as healthcare infrastructure, cultural attitudes, and demographic characteristics. In resource-limited settings, inadequate healthcare infrastructure often results in poor access to essential palliative care services such as pain management, psychosocial support, and trained personnel, thereby limiting improvements in QoL [28,35]. Cultural attitudes also play a significant role; in many Asian and African societies, discussing end-of-life care remains taboo, delaying palliative care interventions, while strong family involvement in these regions enhances holistic care that aligns with cultural values, improving satisfaction and outcomes [29,36]. Additionally, demographic factors such as age, socioeconomic status, and geographic disparities influence access to palliative care, with older, rural, and lower-income populations being disproportionately affected [25,37].

Strengths and limitations of the study

A notable strength of this study is its comprehensive methodology, incorporating subgroup analysis, meta-regression, and sensitivity analysis to identify potential sources of heterogeneity. By accounting for moderators such as study setting, cancer type, and patient category, the study offers valuable insights into the differential impacts of integrated palliative care (IPC). The reliability of the findings is further reinforced by sensitivity analysis and the absence of significant publication bias. However, the study has certain limitations, including considerable heterogeneity (I² = 82.94%) across the included studies, which may complicate the interpretation of the overall effect size. This heterogeneity could stem from differences in healthcare settings, such as resource availability, infrastructure, and access to IPC services, limiting the generalizability of the results. Furthermore, variability in IPC implementation, shaped by cultural, economic, and systemic factors, may also contribute to the observed outcome differences. Another limitation is the underrepresentation of studies from Asia and Africa, with only one study included from these regions. This limited sample size may have influenced the finding that IPC had a more significant impact in these regions, and caution is advised when interpreting this result given the potential for regional variability.

Conclusion and recommendation

This study demonstrates a significant improvement in quality of life for cancer patients receiving integrated palliative care compared to standard care. Subgroup analysis revealed that the benefits are particularly notable in Asia and Africa, among lung cancer patients, and in newly diagnosed individuals, highlighting regional disparities in healthcare and the heavy symptom burden associated with certain cancer types. Prioritizing the early implementation of palliative care is essential to optimize patient outcomes and enhance quality of life across diverse populations. Policymakers can leverage these results to advocate for the integration of standardized palliative care protocols within existing cancer care systems, ensuring equitable access to IPC services, particularly in resource-limited settings. The study underscores the need to strengthen palliative care infrastructure to reduce disparities in care delivery and improve patient well-being. Future randomized controlled trials (RCTs) should focus on implementing standardized IPC protocols to reduce variability and explore which specific components, such as symptom control, psychosocial support, or spiritual care, yield the most significant improvements in quality of life.

Supporting information

S1 Text

S1 Fig. The Cochrane RoB 2 tool provides a detailed assessment across various domains to compare the effects of integrated palliative care versus standard care on cancer patients’ quality of life. S1 Table. The findings follow the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines, available as a supplementary file. S2 Table. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist is used to evaluate the comparative impact of integrated palliative care vs. standard care on the quality of life in cancer patients. S3 Table. Dataset for a study conducted on Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials. S4 Table. A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.

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pone.0321586.s001.zip^{(1,001.5KB, zip)}

Abbreviations

CI: Confidence Interval
ICP: Integrated Palliative Care
QoL: Quality of Life
PRISMA: Preferred Reporting Items for Systematic Review and Meta-analysis
RCTs: Randomized Control Trials
SMD: Standardized Mean Difference

Data Availability

All relevant data are within the article and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.;

References

1.Siegel RL, Miller KD, Jemal A, Ward E, Kohler BA, Parker D, et al. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(1):7–33. doi: 10.3322/caac.21708 [DOI] [PubMed] [Google Scholar]
2.Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–42. doi: 10.1056/NEJMoa1000678 [DOI] [PubMed] [Google Scholar]
3.Kaasa S. Integration of palliative care in cancer care: the European association for palliative care (EAPC) position paper. European J Cancer. 2018;94:103–10. [Google Scholar]
4.Padgett LS, et al. Integrating early palliative care into cancer care: a qualitative analysis of implementation models, barriers, and strategies in community settings. American Soc Clin Oncol. 2014. [Google Scholar]
5.Goudarzi R, Heidarzadeh A. Effects of integrated palliative care on pain and quality of life in cancer patients: a systematic review. BMC Palliative Care. 2020;19(1):16. doi: 10.1186/s12885-020-07007-632013949 [DOI] [Google Scholar]
6.Dawson K, Cartwright C, Smith T. The impact of palliative care on cancer patients’ quality of life: a systematic review. Supportive Care in Cancer. 2020;28(5):2237–54. doi: 10.1007/s00520-019-05068-3 [DOI] [Google Scholar]
7.Vick JB, Ornstein KA, Szanton SL, Dy SM, Wolff JL. Does caregiving strain increase as patients with and without dementia approach the end of life?. J Pain Symptom Manage. 2019;57(2):199-208.e2. doi: 10.1016/j.jpainsymman.2018.11.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
8.Seymour JE, et al. The impact of palliative care on patients’ quality of life: a systematic review of the evidence. Palliative Medicine. 2010;24(3):240. doi: 10.1177/0269216309359281 [DOI] [Google Scholar]
9.Barker TH, Stone JC, Sears K, Klugar M, Tufanaru C, Leonardi-Bee J, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21(3):494–506. doi: 10.11124/JBIES-22-00430 [DOI] [PubMed] [Google Scholar]
10.Hildenbrand JD. Patient-reported distress as an early waring sign of unmet palliative care needs and increased healthcare utilization in patients with advanced cancer. Supportive Care in Cancer. 2022:1–9. [DOI] [PubMed] [Google Scholar]
11.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi: 10.1371/journal.pmed.1000097 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111. doi: 10.1002/jrsm.12 [DOI] [PubMed] [Google Scholar]
13.Rücker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I(2) in assessing heterogeneity may mislead. BMC Med Res Methodol. 2008;8:79. doi: 10.1186/1471-2288-8-79 [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Franciosi V, Maglietta G, Degli Esposti C, Caruso G, Cavanna L, Bertè R, et al. Early palliative care and quality of life of advanced cancer patients-a multicenter randomized clinical trial. Ann Palliat Med. 2019;8(4):381–9. doi: 10.21037/apm.2019.02.07 [DOI] [PubMed] [Google Scholar]
16.Bakitas MA, Tosteson TD, Li Z, Lyons KD, Hull JG, Li Z, et al. Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol. 2015;33(13):1438–45. doi: 10.1200/JCO.2014.58.6362 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Vanbutsele G, Pardon K, Van Belle S, Surmont V, De Laat M, Colman R, et al. Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trial. Lancet Oncol. 2018;19(3):394–404. doi: 10.1016/S1470-2045(18)30060-3 [DOI] [PubMed] [Google Scholar]
18.Groenvold M, Petersen MA, Damkier A, Neergaard MA, Nielsen JB, Pedersen L, et al. Randomised clinical trial of early specialist palliative care plus standard care versus standard care alone in patients with advanced cancer: the danish palliative care trial. Palliat Med. 2017;31(9):814–24. doi: 10.1177/0269216317705100 [DOI] [PubMed] [Google Scholar]
19.Slama O, Pochop L, Sedo J, Svancara J, Sedova P, Svetlakova L, et al. Effects of early and systematic integration of specialist palliative care in patients with advanced cancer: randomized controlled trial PALINT. J Palliat Med. 2020;23(12):1586–93. doi: 10.1089/jpm.2019.0697 [DOI] [PubMed] [Google Scholar]
20.Vanbutsele G, Van Belle S, Surmont V, De Laat M, Colman R, Eecloo K, et al. The effect of early and systematic integration of palliative care in oncology on quality of life and health care use near the end of life: a randomised controlled trial. Eur J Cancer. 2020;124:186–93. doi: 10.1016/j.ejca.2019.11.009 [DOI] [PubMed] [Google Scholar]
21.Reid EA, Abathun E, Diribi J, Mamo Y, Wondemagegnhu T, Hall P, et al. Early palliative care in newly diagnosed cancer in Ethiopia: feasibility randomised controlled trial and cost analysis. BMJ Support Palliat Care. 2022;14(e1):e504–e507. doi: 10.1136/spcare-2022-003996 [DOI] [PubMed] [Google Scholar]
22.Temel JS, Greer JA, El-Jawahri A, Pirl WF, Park ER, Jackson VA, et al. Effects of early integrated palliative care in patients with lung and GI cancer: a randomized clinical trial. J Clin Oncol. 2017;35(8):834–41. doi: 10.1200/JCO.2016.70.5046 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Chen M, Yu H, Yang L, Yang H, Cao H, Lei L, et al. Combined early palliative care for non-small-cell lung cancer patients: a randomized controlled trial in Chongqing, China. Front Oncol. 2023;13:1184961. doi: 10.3389/fonc.2023.1184961 [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Connor SR, Downing J, Marston J. Estimating the global need for palliative care for children: a cross-sectional analysis. J Pain Symptom Management. 2020;60(1):115–21. [DOI] [PubMed] [Google Scholar]
25.Hui D, Kim SH, Roquemore J, Dev R, Chisholm G, Bruera E. Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients. Cancer. 2014;120(11):1743–9. doi: 10.1002/cncr.28628 [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Haun MW, Estel S, Rücker G, Friederich H-C, Villalobos M, Thomas M, et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev. 2017;6(6):CD011129. doi: 10.1002/14651858.CD011129.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Systematic reviews of etiology and risk. JBI Manual for Evidence Synthesis. 2020. [Google Scholar]
28.Knaul FM, Farmer PE, Krakauer EL, De Lima L, Bhadelia A, Jiang Kwete X, et al. Alleviating the access abyss in palliative care and pain relief-an imperative of universal health coverage: the lancet commission report. Lancet. 2018;391(10128):1391–454. doi: 10.1016/S0140-6736(17)32513-8 [DOI] [PubMed] [Google Scholar]
29.Rhee JY, Garralda E, Torrado C, Blanco S. Palliative care in Asia: a cross-regional analysis of needs and barriers. The Lancet Global Health. 2018;6(8):e843–9.30012266 [Google Scholar]
30.Parikh RB, et al. Early specialty palliative care—translating data in oncology into practice. Journal Name. 2013;2347–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Higginson IJ, Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M, et al. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med. 2014;2(12):979–87. doi: 10.1016/S2213-2600(14)70226-7 [DOI] [PubMed] [Google Scholar]
32.Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96–112. doi: 10.1200/JCO.2016.70.1474 [DOI] [PubMed] [Google Scholar]
33.Kochovska S, Ferreira DH, Luckett T, Phillips JL, Currow DC. Earlier multidisciplinary palliative care intervention for people with lung cancer: a systematic review and meta-analysis. Transl Lung Cancer Res. 2020;9(4):1699–709. doi: 10.21037/tlcr.2019.12.18 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Mancuso CA, Author2 F, Author3 F, Author4 F, Author5 F. Effect of a 12-week physical therapy program on disability and quality of life in patients with chronic low back pain: a randomized controlled trial. J Rehabilitation Research and Development. 2014;51(5):567–75. [Google Scholar]
35.Cleary J, Ddungu H, Distelhorst SR, Ripamonti C. Pain management for resource-limited settings. WHO Publications; 2013. [Google Scholar]
36.Yamaguchi T, Kuriya M, Morita T, Miyashita M. Family satisfaction with end-of-life care in advanced cancer patients: A nationwide study in Japan. Annals of Oncology. 2017;28(10):2312-2317.28655213 [Google Scholar]
37.Luyirika EB, Namisango E, Garanganga E, Mwebesa E. A palliative care initiative improves quality of life for cancer patients in Uganda. African Health Sciences. 2016;16(3):693–700. doi: 10.4314/ahs.v16i3.37 [DOI] [Google Scholar]

PLoS One. 2025 Apr 10;20(4):e0321586. doi: 10.1371/journal.pone.0321586.r001

Author response to Decision Letter 0

9 Oct 2024

PLoS One. doi: 10.1371/journal.pone.0321586.r002

Decision Letter 0

Usama Waqar

11 Dec 2024

PONE-D-24-43910Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled TrialsPLOS ONE

Dear Dr. Getie,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the Impact of integrated palliative care (IPC) in comparison to standard care (SC) on the quality of life (QoL) of different cancer patients across different stage and settings. The authors have reported that IPC is statistically associated with improved QoL, especially among lung cancer patients, patients from Africa, and newly diagnosed patients.

I have the following comments:

1. The authors emphasize the need for this study due to the lack of high-quality evidence supporting the integration of integrated palliative care (IPC) in cancer management, despite varying findings across studies. However, a literature search reveals a study by Xu S. et al., titled “The effects of integrated palliative care on quality of life and psychological distress in patients with advanced cancer: a systematic review and meta-analysis.” This study highlights the positive effects of IPC on patients' quality of life (QoL) and psychological well-being. It also examines multiple types of cancer, including hematological malignancies, similar to the author’s study. Additionally, it addresses variations in QoL improvement across different IPC models. The authors should acknowledge this evidence and clearly define the specific gap in the literature that their study aims to address.

2. The authors have mentioned in their “search strategy” that only articles published in English will be included. However, “eligibility criteria” mentions that there will be no restrictions on language. Similarly, authors mention in their “search strategy” that articles from inception will be included, while in “data collection and quality assessment” study mentions RCTs published in last ten years will be included. The authors need to address these inconsistencies.

3. The authors need to add definitions and explicit details to strengthen their study:

a. The authors need to clearly state the definition of IPC and SC which they used for their inclusion along with the IPC model they accepted.

b. The authors should also define the threshold they used to define high, moderate, or low risk of bias.

c. The authors need to define how they determined the advanced stage of cancer or if they accepted included study authors’ definition. Moreover, the authors have written “all” as the site of cancer in table 1 but did not explain clearly with a footnote that “all” defines as cancer involving lung, gastrointestinal, breast, and reproductive organs.

4. The authors need to add more details in table 1 to improve it including the phase of the RCT and the QoL tool(s) used by it.

5. While authors have explained their screening process along with two independent reviewer policy to reduce bias, the authors have failed to mention if a software, such as Covidence, was used for this process.

6. While the study methodology mentions the plan for risk of bias and quality assessment of included studies, the authors have not conducted and represented the quality assessment in results, explained them in discussion, or conducted associated analysis after excluding low quality RCTs.

7. Figure 3 represents USA’s standard mean difference (SMD) as significant with value of 4.84 [2.49-7.19]. However, authors have not represented this finding in their results or explained it in their discussion. Moreover, authors have not represented studies from Asia in their figure 3.

8. The authors have mentioned, “The studies consistently showed a positive impact of IPC on patient satisfaction, symptom management, and overall quality of life, especially in advanced cancer stages”. However, later it is mentioned, “These findings suggest that the integration of palliative care has a more pronounced impact on patients from Africa, those with lung cancer, and newly diagnosed individuals.” The authors should explain this finding in more detail.

9. The authors explain that African patients showed most benefit for IPC on QoL with other evidence also supporting more pronounced effects of palliative care in low-resource settings. However, this explanation is refuted by authors’ own positive finding for USA. The authors should highlight this and explain their findings.

10. The authors find that lung cancer is significantly associated with improved outcomes with evidence showing such trend among advanced lung cancer patients. However, the included RCT included newly diagnosed patients. The authors should highlight this difference. Moreover, they can cite a systematic review by Kochovska S et al. (PMID: 32953543) which also IPC use early in lung cancer.

Reviewer #2: Summary:

This manuscript provides a well-conducted systematic review and meta-analysis by analyzing RCTs across various geographic regions and cancer types. It provides a comprehensive and globally relevant perspective on IPC's benefits, specially in resource-limited settings. The study is methodologically rigorous and provides a valuable contribution to evidence-based practice in palliative oncology.

Revision:

1. While the authors conduct subgroup and sensitivity analyses to account for heterogeneity, a more detailed discussion on the variables leading to high heterogeneity (I² = 82.94%) could strengthen the interpretation, particularly around the variability in IPC implementation and patient demographics.

2. To improve clarity, explicitly define each subgroup for example patient categories (e.g., newly diagnosed vs. advanced) and summarize findings for each subgroup analysis.

3. Expand the limitations section to acknowledge that variations in healthcare settings and IPC implementation could limit generalizability of results

4. Proof read the manuscript for few minor grammatical errors and clarity

5. Suggest directions for future RCTs for example using a standardized IPC protocol to reduce variability and explore specific IPC components which has the greatest impact on QoL.

Reviewer #3: The authors conducted a systematic review and meta-analysis comparing the impact of integrated palliative care vs. standard care on the quality of life in cancer patients. The authors 9 randomized controlled trials showcasing an increase in quality of life with integrated palliative care. Stratified analysis by continent, patient population, and cancer type demonstrated consistency of the results. The authors concluded that through integrating palliative care, quality of life for all cancer patients can be improved significantly. I congratulate the authors on a well conducted study.

I have a few comments:

1. Authors should provide rationale for choosing only RCTs for their systematic review and meta-analysis.

2. Page 3, 3rd para of introduction, the authors mention that some studies show benefit of IPC while others do not. The reference of this statement is a single student showing benefit.

The authors have explained the knowledge gap and created the need for a systematic review. However, there is a need to cite studies showing no benefit of IPC considering the statement.

3. Several lines in the first para of discussion lack citations.

4. 2nd line of 2nd para of discussion citing a study by Davis et al. lacks a citation.

5. The authors should attempt to explain why low resource settings have a greater impact of integrated palliative care in the discussion section.

6. Similarly, in the para on page 10 explaining the impact of IPC on lung cancer should be expanded to talk briefly about the reasons behind this finding.

7. The authors should expand on the discussion section’s recommendation paragraph on future implications. How can the results of this study be used for policy making or improving cancer care guidelines? This has been briefly mentioned at the end of the manuscript but needs further elaboration.

8. The authors reported that the impact of IPC was more pronounced in Africa. There is only 1 study from Africa included in this review. Could this have influenced the results? Please include this in limitations section.

9. The authors should replace the word USA with North America if they are trying to compare continents (as mentioned in the manuscript several times)

10. The authors show a comparison of newly diagnosed vs. advanced cancer patients in figure 5. Would any of these newly diagnosed patients be considered advanced if they have Stage IV disease? This categorization needs rewording.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

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PLoS One. 2025 Apr 10;20(4):e0321586. doi: 10.1371/journal.pone.0321586.r003

Author response to Decision Letter 1

21 Dec 2024

Response to Reviewers

PONE-D-24-43910

Title: Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

1. Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Authors response 1: Thank you for your email regarding the review of our manuscript titled. We appreciate the time and effort of the reviewers and editorial team in evaluating our work and providing constructive feedback. We are pleased that you find our manuscript to have merit, and we are committed to addressing the reviewers' comments and concerns to enhance the quality and impact of our study. We carefully revised the manuscript and incorporated the feedback provided.

2. Please submit your revised manuscript by Jan 25 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Authors response 2: Thank you for providing the timeline for submitting the revised version of our manuscript. We acknowledge the deadline of January 25, 2025, at 11:59 PM and we submitted the revised manuscript within this timeframe.

3. Please include the following items when submitting your revised manuscript:

3.1. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

Authors response 3.1: Thank you for providing the detailed feedback from the academic editor and reviewers regarding our manuscript. We have carefully considered each comment and suggestion and have revised the manuscript accordingly to address the concerns raised and we attached our rebuttal Letter, titled “Response to Reviewers,” where we have provided a detailed, point-by-point response to all comments.

3.2. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

Authors response 3.2: Thank you for the opportunity to revise our manuscript. We have made the necessary changes in response to the comments and suggestions provided by the academic editor and reviewers. As requested, we have prepared a marked-up version of the manuscript that highlights all revisions using track changes. This file is titled “Revised Manuscript with Track Changes” and has been uploaded as a separate document.

3.3. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Authors response 3.3: Thank you for your instructions regarding the submission of our revised manuscript titled. As requested, we have prepared an unmarked version of the revised manuscript, with all track changes accepted, to reflect the final clean version. This file is titled “Manuscript” and has been uploaded as a separate document.

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

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Authors response 1: Thank you for the reminder regarding PLOS ONE’s style and file naming requirements. We ensured that our revised manuscript and all associated files comply fully with the journal's guidelines.

2. We note that your Data Availability Statement is currently as follows: [Not applicable]. Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition). For example, authors should submit the following data:

� The values behind the means, standard deviations and other measures reported;

� The values used to build graphs;

� The points extracted from images for analysis.

Authors do not need to submit their entire data set if only a portion of the data was used in the reported study. If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.

Authors response 2: Thank you for your reminder regarding the dataset. We would like to confirm that the authors have prepared a dataset in Microsoft Excel, which was specifically designed as an extraction sheet. This sheet was used to systematically collect and organize all relevant data from the studies included in our analysis. To ensure transparency and facilitate further understanding of our research process, we have provided this Microsoft Excel file as a relevant data repository document alongside our manuscript. Additionally, most of the data referenced in the manuscript can be found in Table 1. Please do not hesitate to reach out if additional clarifications or modifications to the dataset are required.

3. As required by our policy on Data Availability, please ensure your manuscript or supplementary information includes the following:

� A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.

� For every excluded study, the table should list the reason(s) for exclusion.

� If any of the included studies are unpublished, include a link (URL) to the primary source or detailed information about how the content can be accessed.

Authors response 3: Thank you for providing the instructions regarding the submission of a detailed table of studies identified in our literature search. In response, we have prepared a comprehensive document to meet your requirements. The document includes a numbered table summarizing all studies identified during the search, detailing both included and excluded studies and found in the relevant data repository document. However, due to the large volume of articles excluded for various reasons, it was not feasible to present all excluded studies in a single table. Instead, we have provided a representative summary, clearly listing the reasons for exclusion (e.g., not meeting inclusion criteria, irrelevant outcomes, duplicate data) to ensure transparency and adherence to systematic review reporting standards. Additionally, we confirm that our review did not include unpublished studies. Should further clarification or adjustments to the document be required, please feel free to let us know.

4. A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis. The table must include the following information for each study:

� Name of data extractors and date of data extraction

� Confirmation that the study was eligible to be included in the review.

� All data extracted from each study for the reported systematic review and/or meta-analysis that would be needed to replicate your analyses.

Authors response 4: Thank you for your instructions regarding the submission of a detailed data extraction table. In response, we have prepared and uploaded a comprehensive table that includes all relevant information extracted from the primary research sources used in our systematic review and/or meta-analysis. The table addresses all specified requirements as follows, including the name of data extractor and date of extraction, study eligibility confirmation, and extracted data for analysis replication. The data extraction table has been uploaded as table file “Table 1”

5. If applicable for your analysis, a table showing the completed risk of bias and quality/certainty assessments for each study or outcome. Please ensure this is provided for each domain or parameter assessed. For example, if you used the Cochrane risk-of-bias tool for randomized trials, provide answers to each of the signaling questions for each study. If you used GRADE to assess certainty of evidence, provide judgements about each of the quality of evidence factor. This should be provided for each outcome.

Authors response 5: Thank you for your guidance regarding the submission of risk of bias and quality/certainty assessments for the studies included in our analysis. In response, we have diligently prepared the requested table, which includes the following: For the studies assessed using the Cochrane Risk-of-Bias tool (for randomized trials), we have provided responses to each signaling question for every study included in the review. The table clearly presents the risk of bias for each evaluated domain and is submitted as a supplementary file titled "Risk of Bias Assessment."

6. An explanation of how missing data were handled.

Authors response 6: Thank you for your inquiry regarding how we handled missing data in our analysis. We want to assure you that we carefully addressed the issue of missing data and implemented appropriate strategies to manage it, following established research practices. This included identifying and documenting missing data, as well as conducting sensitivity analyses to assess its impact.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Authors response 1: We appreciate your confirmation that our study adequately addresses the question, "Is the manuscript technically sound, and do the data support the conclusions?"

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Authors response 2: We appreciate your confirmation that our study adequately addresses the question, "has the statistical analysis been performed appropriately and rigorously?"

3. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

Authors response 3: Thank you for approving the dataset. We confirm that the authors have prepared a Microsoft Excel file specifically designed as a data extraction sheet. This sheet was systematically used to collect and organize relevant data from the studies included in our analysis. To ensure transparency and enhance understanding of our research process, we have included this Excel file as a supplementary document alongside the manuscript. Additionally, most of the data referenced in the manuscript can be found in Table 1. Please feel free to contact us if further clarifications or modifications to the dataset are needed.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

5. Review Comments to the Author

I have the following comments:

Authors response 1: Thank you for bringing the study by Xu S. et al. to our attention. We acknowledge that this work highlights the positive effects of Integrated Palliative Care (IPC) on quality of life (QoL) and psychological well-being in patients with advanced cancer and examines variations in QoL improvement across IPC models. However, while their study provides valuable insights, our review aims to address specific gaps that were not thoroughly explored, including the comparative impact of IPC versus standard care across diverse geographic settings and populations. To clarify the uniqueness of our study, we have now included a discussion of the findings by Xu S. et al. in the introduction and elaborated on how our review builds upon and complements their work. Specifically, our study focuses on synthesizing evidence from randomized controlled trials to evaluate the global impact of IPC on QoL, with a particular emphasis on regional variations and the inclusion of studies published after Xu S. et al.'s review. We have updated the manuscript accordingly and appreciate your suggestion to refine the gap statement, ensuring the d

Attachment

Submitted filename: Response to Reviewers.docx

pone.0321586.s003.docx^{(42KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0321586.r004

Decision Letter 1

Usama Waqar

2 Mar 2025

PONE-D-24-43910R1Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

PLOS ONE

Dear Dr. Getie,

Please address the editorial comment on the follow-up intervals for QoL assessment in included studies.

Please submit your revised manuscript by Apr 16 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The mentioned outcome is QoL. Different studies may have measured QoL at different follow-up intervals. Did you focus on QoL at a specific follow-up interval after IPC vs. SC? How did you pool QoL data from multiple studies with different follow-up intervals in your meta-analyses? Please address in the Methods section in the Outcome heading or the statistical analysis plan.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Reviewer #2: (No Response)

Reviewer #4: I applaud the authors on their rigorous edits, which have satisfied any concerns that I may have had. I believe this manuscript makes a valuable contribution to the literature.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

Reviewer #4: No

**********

PLoS One. 2025 Apr 10;20(4):e0321586. doi: 10.1371/journal.pone.0321586.r005

Author response to Decision Letter 2

4 Mar 2025

Response to Reviewers

PONE-D-24-43910R1

Title: Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors response 1: Thank you for your email regarding the review of our manuscript. We appreciate the time and effort of the reviewers and editorial team in evaluating our work and providing constructive feedback. We are pleased that you find our manuscript to have merit, and we are committed to addressing the reviewers' comments and concerns to enhance the quality and impact of our study. We carefully revised the manuscript and incorporated the feedback provided.

2. Please address the editorial comment on the follow-up intervals for QoL assessment in included studies.

Authors response 2: Thank you for your comment. We have addressed the follow-up intervals for QoL assessment in the included studies in the revised manuscript in the method section, providing clarification on the methods used to handle varying follow-up times.

3. Please submit your revised manuscript by Apr 16 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Authors response 3: Thank you for providing the timeline for submitting the revised version of our manuscript. We acknowledge the deadline of Apr 16 2025 11:59PM and we submitted the revised manuscript within this timeframe.

4. Please include the following items when submitting your revised manuscript:

4.1. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

Authors response 4.1: Thank you for providing the detailed feedback from the academic editor and reviewers regarding our manuscript. We have carefully considered each comment and suggestion and have revised the manuscript accordingly to address the concerns raised and we attached our rebuttal Letter, titled “Response to Reviewers,” where we have provided a detailed, point-by-point response to all comments.

4.2. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

Authors response 4.2: Thank you for the opportunity to revise our manuscript. We have made the necessary changes in response to the comments and suggestions provided by the academic editor and reviewers. As requested, we have prepared a marked-up version of the manuscript that highlights all revisions using track changes. This file is titled “Revised Manuscript with Track Changes” and has been uploaded as a separate document.

4.3. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Authors response 4.3: Thank you for your instructions regarding the submission of our revised manuscript titled. As requested, we have prepared an unmarked version of the revised manuscript, with all track changes accepted, to reflect the final clean version. This file is titled “Manuscript” and has been uploaded as a separate document.

Journal Requirements:

1. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors response 1: Thank you for your feedback. We have thoroughly reviewed the reference list and made necessary corrections.

Additional Editor Comments:

2. The mentioned outcome is QoL. Different studies may have measured QoL at different follow-up intervals. Did you focus on QoL at a specific follow-up interval after IPC vs. SC? How did you pool QoL data from multiple studies with different follow-up intervals in your meta-analyses? Please address in the Methods section in the Outcome heading or the statistical analysis plan.

Authors response 2: Thank you, we have included the information in the Methods section under the Outcome heading as “To pool QoL data from studies with varying follow-up intervals, we used random-effects models, which effectively account for differences in follow-up durations and the inherent variability across studies. This statistical approach adjusts for the fact that each study may measure QoL at different time points, allowing for a more accurate estimation of the overall effect. By incorporating random effects, we were able to address both within-study and between-study variability, ensuring that our pooled estimate appropriately reflects the diversity of follow-up intervals and study designs”

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict-of-interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

Authors response 1: Thank you

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

Reviewer #4: Yes

Authors response 2: Thank you

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #4: Yes

Authors response 3: Thank you

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

Reviewer #4: Yes

Authors response 4: Thank you

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

Reviewer #4: Yes

Authors response 5: Thank you

6. Review Comments to the Author

Reviewer #2: (No Response)

Reviewer #4: I applaud the authors on their rigorous edits, which have satisfied any concerns that I may have had. I believe this manuscript makes a valuable contribution to the literature.

Authors response 6: Thank you

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #4: No

Attachment

Submitted filename: Response_to_Reviewers_auresp_2.docx

pone.0321586.s004.docx^{(22.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0321586.r006

Decision Letter 2

Usama Waqar

5 Mar 2025

PONE-D-24-43910R2Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled TrialsPLOS ONE

Dear Dr. Getie,

Please submit your revised manuscript by Apr 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Additional Editor Comments:

Random effects model only accounts for heterogeniety, which refers to differences in effects, i.e., odds ratios, risk ratios, etc, being estimated in the different studies included in a meta-analysis. It does not account for differences in follow-up intervals of individual studies.

Please see the following text from the Cochrane Handbook: 9.5.4 Incorporating heterogeneity into random-effects models.

"A random-effects meta-analysis model involves an assumption that the effects being estimated in the different studies are not identical, but follow some distribution. The model represents our lack of knowledge about why real, or apparent, intervention effects differ by considering the differences as if they were random. The centre of this distribution describes the average of the effects, while its width describes the degree of heterogeneity."

If the authors have not accounted for differences in follow up interval, this is a substantial error with the study design. Studies with short-term follow up may underestimate impact of different modalities on QoL; they cannot be merged with studies assessing QoL at larger intervals straight up. The authors should report follow up intervals at which QoL was assessed by individual studies in their Characteristics of Included Studies Table, then perform either of the following approach that aligns mostly with the variations in follow up intervals in the included studies (cannot directly assess as the authors have not provided this data:

1. Stratified analysis by follow-up duration

2. Meta-regression incorporating follow-up interval as an effect size

3. Sensitivity analyses excluding studies with very short or very long follow up intervals and pooling data from studies with similar follow-up intervals.

[Note: HTML markup is below. Please do not edit.]

PLoS One. 2025 Apr 10;20(4):e0321586. doi: 10.1371/journal.pone.0321586.r007

Author response to Decision Letter 3

6 Mar 2025

Response to Reviewers

PONE-D-24-43910R1

Title: Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

2. Please submit your revised manuscript by Apr 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Authors response 2: Thank you for providing the timeline for submitting the revised version of our manuscript. We acknowledge the deadline of Apr 16 2025 11:59PM and we submitted the revised manuscript within this timeframe.

3. Please include the following items when submitting your revised manuscript:

3.1. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

3.2. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

3.3. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Additional Editor Comments:

Please see the following text from the Cochrane Handbook: 9.5.4 Incorporating heterogeneity into random-effects models.

1. Stratified analysis by follow-up duration

2. Meta-regression incorporating follow-up interval as an effect size

3. Sensitivity analyses excluding studies with very short or very long follow up intervals and pooling data from studies with similar follow-up intervals.

Authors response: Thank you for your suggestion. We have now included the follow-up intervals for QoL assessments in the Characteristics of Included Studies Table (Table 1). Among the included studies, six had a 3-month follow-up period, two had a 6-month period, and one had a 2-month follow-up. Based on this data, we conducted a stratified analysis, which is presented in Fig 6, with the findings discussed accordingly. Additionally, we performed a meta-regression that incorporated the follow-up interval as an effect size, which can be found in the results section. Furthermore, a sensitivity analysis was conducted to account for variations in follow-up durations across studies.

Attachment

Submitted filename: Response_to_Reviewers_auresp_3.docx

pone.0321586.s005.docx^{(23.3KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0321586.r008

Decision Letter 3

Usama Waqar

9 Mar 2025

Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

PONE-D-24-43910R3

Dear Dr. Getie,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0321586.r009

Acceptance letter

Usama Waqar

PONE-D-24-43910R3

PLOS ONE

Dear Dr. Getie,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

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* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Usama Waqar

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Text

(ZIP)

pone.0321586.s001.zip^{(1,001.5KB, zip)}

Attachment

Submitted filename: Response to Reviewers.docx

pone.0321586.s003.docx^{(42KB, docx)}

Attachment

Submitted filename: Response_to_Reviewers_auresp_2.docx

pone.0321586.s004.docx^{(22.4KB, docx)}

Attachment

Submitted filename: Response_to_Reviewers_auresp_3.docx

pone.0321586.s005.docx^{(23.3KB, docx)}

Data Availability Statement

All relevant data are within the article and its Supporting Information files.

[pone.0321586.ref001] 1.Siegel RL, Miller KD, Jemal A, Ward E, Kohler BA, Parker D, et al. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(1):7–33. doi: 10.3322/caac.21708 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref002] 2.Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–42. doi: 10.1056/NEJMoa1000678 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref003] 3.Kaasa S. Integration of palliative care in cancer care: the European association for palliative care (EAPC) position paper. European J Cancer. 2018;94:103–10. [Google Scholar]

[pone.0321586.ref004] 4.Padgett LS, et al. Integrating early palliative care into cancer care: a qualitative analysis of implementation models, barriers, and strategies in community settings. American Soc Clin Oncol. 2014. [Google Scholar]

[pone.0321586.ref005] 5.Goudarzi R, Heidarzadeh A. Effects of integrated palliative care on pain and quality of life in cancer patients: a systematic review. BMC Palliative Care. 2020;19(1):16. doi: 10.1186/s12885-020-07007-632013949 [DOI] [Google Scholar]

[pone.0321586.ref006] 6.Dawson K, Cartwright C, Smith T. The impact of palliative care on cancer patients’ quality of life: a systematic review. Supportive Care in Cancer. 2020;28(5):2237–54. doi: 10.1007/s00520-019-05068-3 [DOI] [Google Scholar]

[pone.0321586.ref007] 7.Vick JB, Ornstein KA, Szanton SL, Dy SM, Wolff JL. Does caregiving strain increase as patients with and without dementia approach the end of life?. J Pain Symptom Manage. 2019;57(2):199-208.e2. doi: 10.1016/j.jpainsymman.2018.11.004 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref008] 8.Seymour JE, et al. The impact of palliative care on patients’ quality of life: a systematic review of the evidence. Palliative Medicine. 2010;24(3):240. doi: 10.1177/0269216309359281 [DOI] [Google Scholar]

[pone.0321586.ref009] 9.Barker TH, Stone JC, Sears K, Klugar M, Tufanaru C, Leonardi-Bee J, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21(3):494–506. doi: 10.11124/JBIES-22-00430 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref010] 10.Hildenbrand JD. Patient-reported distress as an early waring sign of unmet palliative care needs and increased healthcare utilization in patients with advanced cancer. Supportive Care in Cancer. 2022:1–9. [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref011] 11.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi: 10.1371/journal.pmed.1000097 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref012] 12.Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111. doi: 10.1002/jrsm.12 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref013] 13.Rücker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I(2) in assessing heterogeneity may mislead. BMC Med Res Methodol. 2008;8:79. doi: 10.1186/1471-2288-8-79 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref014] 14.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. doi: 10.1136/bmj.315.7109.629 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref015] 15.Franciosi V, Maglietta G, Degli Esposti C, Caruso G, Cavanna L, Bertè R, et al. Early palliative care and quality of life of advanced cancer patients-a multicenter randomized clinical trial. Ann Palliat Med. 2019;8(4):381–9. doi: 10.21037/apm.2019.02.07 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref016] 16.Bakitas MA, Tosteson TD, Li Z, Lyons KD, Hull JG, Li Z, et al. Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol. 2015;33(13):1438–45. doi: 10.1200/JCO.2014.58.6362 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref017] 17.Vanbutsele G, Pardon K, Van Belle S, Surmont V, De Laat M, Colman R, et al. Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trial. Lancet Oncol. 2018;19(3):394–404. doi: 10.1016/S1470-2045(18)30060-3 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref018] 18.Groenvold M, Petersen MA, Damkier A, Neergaard MA, Nielsen JB, Pedersen L, et al. Randomised clinical trial of early specialist palliative care plus standard care versus standard care alone in patients with advanced cancer: the danish palliative care trial. Palliat Med. 2017;31(9):814–24. doi: 10.1177/0269216317705100 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref019] 19.Slama O, Pochop L, Sedo J, Svancara J, Sedova P, Svetlakova L, et al. Effects of early and systematic integration of specialist palliative care in patients with advanced cancer: randomized controlled trial PALINT. J Palliat Med. 2020;23(12):1586–93. doi: 10.1089/jpm.2019.0697 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref020] 20.Vanbutsele G, Van Belle S, Surmont V, De Laat M, Colman R, Eecloo K, et al. The effect of early and systematic integration of palliative care in oncology on quality of life and health care use near the end of life: a randomised controlled trial. Eur J Cancer. 2020;124:186–93. doi: 10.1016/j.ejca.2019.11.009 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref021] 21.Reid EA, Abathun E, Diribi J, Mamo Y, Wondemagegnhu T, Hall P, et al. Early palliative care in newly diagnosed cancer in Ethiopia: feasibility randomised controlled trial and cost analysis. BMJ Support Palliat Care. 2022;14(e1):e504–e507. doi: 10.1136/spcare-2022-003996 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref022] 22.Temel JS, Greer JA, El-Jawahri A, Pirl WF, Park ER, Jackson VA, et al. Effects of early integrated palliative care in patients with lung and GI cancer: a randomized clinical trial. J Clin Oncol. 2017;35(8):834–41. doi: 10.1200/JCO.2016.70.5046 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref023] 23.Chen M, Yu H, Yang L, Yang H, Cao H, Lei L, et al. Combined early palliative care for non-small-cell lung cancer patients: a randomized controlled trial in Chongqing, China. Front Oncol. 2023;13:1184961. doi: 10.3389/fonc.2023.1184961 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref024] 24.Connor SR, Downing J, Marston J. Estimating the global need for palliative care for children: a cross-sectional analysis. J Pain Symptom Management. 2020;60(1):115–21. [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref025] 25.Hui D, Kim SH, Roquemore J, Dev R, Chisholm G, Bruera E. Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients. Cancer. 2014;120(11):1743–9. doi: 10.1002/cncr.28628 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref026] 26.Haun MW, Estel S, Rücker G, Friederich H-C, Villalobos M, Thomas M, et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev. 2017;6(6):CD011129. doi: 10.1002/14651858.CD011129.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref027] 27.Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Systematic reviews of etiology and risk. JBI Manual for Evidence Synthesis. 2020. [Google Scholar]

[pone.0321586.ref028] 28.Knaul FM, Farmer PE, Krakauer EL, De Lima L, Bhadelia A, Jiang Kwete X, et al. Alleviating the access abyss in palliative care and pain relief-an imperative of universal health coverage: the lancet commission report. Lancet. 2018;391(10128):1391–454. doi: 10.1016/S0140-6736(17)32513-8 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref029] 29.Rhee JY, Garralda E, Torrado C, Blanco S. Palliative care in Asia: a cross-regional analysis of needs and barriers. The Lancet Global Health. 2018;6(8):e843–9.30012266 [Google Scholar]

[pone.0321586.ref030] 30.Parikh RB, et al. Early specialty palliative care—translating data in oncology into practice. Journal Name. 2013;2347–51. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref031] 31.Higginson IJ, Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M, et al. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med. 2014;2(12):979–87. doi: 10.1016/S2213-2600(14)70226-7 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref032] 32.Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96–112. doi: 10.1200/JCO.2016.70.1474 [DOI] [PubMed] [Google Scholar]

[pone.0321586.ref033] 33.Kochovska S, Ferreira DH, Luckett T, Phillips JL, Currow DC. Earlier multidisciplinary palliative care intervention for people with lung cancer: a systematic review and meta-analysis. Transl Lung Cancer Res. 2020;9(4):1699–709. doi: 10.21037/tlcr.2019.12.18 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0321586.ref034] 34.Mancuso CA, Author2 F, Author3 F, Author4 F, Author5 F. Effect of a 12-week physical therapy program on disability and quality of life in patients with chronic low back pain: a randomized controlled trial. J Rehabilitation Research and Development. 2014;51(5):567–75. [Google Scholar]

[pone.0321586.ref035] 35.Cleary J, Ddungu H, Distelhorst SR, Ripamonti C. Pain management for resource-limited settings. WHO Publications; 2013. [Google Scholar]

[pone.0321586.ref036] 36.Yamaguchi T, Kuriya M, Morita T, Miyashita M. Family satisfaction with end-of-life care in advanced cancer patients: A nationwide study in Japan. Annals of Oncology. 2017;28(10):2312-2317.28655213 [Google Scholar]

[pone.0321586.ref037] 37.Luyirika EB, Namisango E, Garanganga E, Mwebesa E. A palliative care initiative improves quality of life for cancer patients in Uganda. African Health Sciences. 2016;16(3):693–700. doi: 10.4314/ahs.v16i3.37 [DOI] [Google Scholar]

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Comparative Impact of Integrated Palliative Care vs. Standard Care on the Quality of Life in Cancer Patients: A Global Systematic Review and Meta-Analysis of Randomized Controlled Trials

Addisu Getie

Afework Edmealem

Tegene Atamenta Kitaw

Roles

Abstract

Introduction

Method

The study protocols

Search strategy

Eligibility criteria

Outcome measurement of the study

Data collection and quality assessment

Data synthesis and analysis

Ethics approval and consent to participate

Results

Fig 1. PRISMA flow chart diagram on a selection of RCTs done on the comparative impact of integrated palliative care vs. standard care on the quality of life in cancer patients.

Study characteristics

Table 1. Study characteristics on RCTs done to evaluate the comparative impact of integrated palliative care vs. standard care on the quality of life in cancer patients.

Risk of bias and quality assessment

Meta-analysis

Impact of integrated palliative care.

Fig 2. Forest plot using a random-effects model illustrating the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Heterogeneity and investigation of the source of heterogeneity.

Fig 3. Forest plot using a random-effects model illustrating sub-group analysis by continent where RCTs were conducted to show the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Fig 4. Forest plot using a random-effects model illustrating sub-group analysis by site of cancer to show the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Fig 5. Forest plot using a random-effects model illustrating sub-group analysis by patient category to show the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Fig 6. Forest plot using a random-effects model illustrating sub-group analysis by follow up duration to show the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Fig 7. Sensitivity analysis utilizing a random-effects model to demonstrate the impact of a leave-one-out estimate.

Publication bias.

Fig 8. Funnel plot with 95% confidence limits illustrating the distribution of the included RCTs in a study examining the comparative effects of integrated palliative care versus standard care on the quality of life in cancer patients.

Discussion

Strengths and limitations of the study

Conclusion and recommendation

Supporting information

Abbreviations

Data Availability

Funding Statement

References

Author response to Decision Letter 0

Decision Letter 0

Usama Waqar

Roles

Author response to Decision Letter 1

Decision Letter 1

Usama Waqar

Roles

Author response to Decision Letter 2

Decision Letter 2

Usama Waqar

Roles

Author response to Decision Letter 3

Decision Letter 3

Usama Waqar

Roles

Acceptance letter

Usama Waqar

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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